Decurarization After Thoracic Anesthesia using sugammadex compared to neostigmine (DATA trial): a multicenter randomized double-blinded controlled trial

Background Thoracic surgery is a high-risk surgery especially for the risk of postoperative pulmonary complications. Postoperative residual paralysis has been shown to be a risk factor for pulmonary complications. Nevertheless, there are few data in the literature concerning the use of neuromuscular blocking agent antagonists in patients undergoing lung surgery. Methods Seventy patients were randomized in three Italian centers to receive sugammadex or neostigmine at the end of thoracic surgery according to the depth of the residual neuromuscular block. The primary outcome was the time from reversal administration to a train-of-four ratio (TOFR) of 0.9. Secondary outcomes were the time to TOFR of 1.0, to extubation, to postanesthesia unit (PACU) discharge, postoperative complications until 30 days after surgery, and length of hospital stay. Results Median time to recovery to a TOFR of 0.9 was significantly shorter in the sugammadex group compared to the neostigmine one (88 vs. 278 s — P < 0.001). The percentage of patients who recovered to a TOFR of 0.9 within 5 min from reversal administration was 94.4% and 58.8% in the sugammadex and neostigmine groups, respectively (P < 0.001). The time to extubation, but not the PACU stay time, was significantly shorter in the sugammadex group. No differences were found between the study groups as regards postoperative complications and length of hospital stay. The superiority of sugammadex in shortening the recovery time was confirmed for both deep/moderate and shallow/minimal neuromuscular block. Conclusions Among patients undergoing thoracic surgery, sugammadex ensures a faster recovery from the neuromuscular block and earlier extubation compared to neostigmine. Supplementary Information The online version contains supplementary material available at 10.1186/s44158-024-00146-6.


Anesthesia protocol
On arrival in the operating room, a thoracic epidural catheter was placed according to local Acute Pain Service protocol.Patient monitoring included electrocardiogram, pulse oximetry, end-tidal carbon dioxide, airway pressures, invasive blood pressure, neuromuscular function monitoring, esophageal temperature.
General anesthesia induction was performed using propofol, remifentanil and rocuronium bromide.
A double lumen tube (DLT) or a single lumen tube with bronchial blocker (BB) were positioned and checked with bronchoscopy.The patients were warmed using a forced air warming blanket and a fluid warmer, if needed.Anesthesia was maintained with remifentanil and inhaled anesthetics or intravenous propofol accordingly to the anesthesiologist's choice.
During two-lung ventilation the tidal volume was set to 8 ml/kg, FiO2=0.5, inspiratory time to 33%, the respiratory rate (RR) was adjusted to maintain the end-tidal CO2 value < 40 mmHg, and positive end-expiratory pressure (PEEP) was set to 5 cmH2O.During OLV the tidal volume was decreased to 4-6 ml/kg and RR adjusted to maintain the end-tidal CO2 < 50 mmHg.At the end of the procedure, after secretions suctioning, an alveolar recruitment maneuver was performed as follows: the ventilator was set in a pressure-controlled modality with an inspiratory pressure of 30 cmH20, the inspiratory time to 50%, RR set to 10 per minute and PEEP = 5 cmH2O for 10 breaths.
Intravenous paracetamol 1 gr and ketorolac 30 mg were administered 30 minutes before the end of the procedure.

TOF-Watch Sx calibration protocol
Eight steps:

Definition of complications
Respiratory infection was defined as the appearance of a new infiltrate on chest radiograph combined with at least two of the following criteria: body temperature greater than 38° C or less than 35.5°C, white blood cell count greater than 12000/mm 3 or less than 4000/mm 3 , presence of purulent sputum. 1 Respiratory failure was defined by the occurrence in the postoperative period of an SpO2 less than 90%, or a PaO2/FiO2 ratio less than 300, 2 a PaCO2 greater than 45 mmHg, 2 the onset of dyspnea with respiratory fatigue and/or use of the accessory muscles of respiration.
Pleural effusion was identified as the appearance in the postoperative period of a glaze on chest radiograph not present on previous radiograms or by the identification by ultrasonography of a collection of non-corpuscular fluid in the pleural cavity. 3Pleural effusion can also be defined by a hypo-/anechogenic zone between the visceral and parietal pleura. 4e presence of pneumothorax was defined as the presence of air in the pleural space diagnosed by chest radiography 5 or by ultrasound imaging showing loss of "gliding sign" or "lung sliding," referring to movement related to breathing. 4eumothorax was defined as the presence of air in the pleural space on chest X-ray or CT scan or the loss of the "gliding sign" or "lung glide," which refers to breath-dependent upward and downward movement on ultrasound examination. 5electasis was defined as opacification of a lobe or lobar segment in question.With a compensatory overinflation of the remaining aerated segments in the affected lobe. 6piration pneumonia was defined as acute lung injury following inhalation of regurgitated gastric contents. 7onchospasm was defined as a newly detected expiratory wheeze and treated with bronchodilators. 1

Details on Trial Interruption
The recruitment of patients was prematurely terminated in 2020 by the scientific committee because it was deemed very difficult to reach the established sample size due to the overall slow recruitment rate and the onset of the COVID-19 pandemic.
A post-hoc Conditional Power was calculated assuming that the mean difference in the primary outcome between the two study groups (time from reversal administration to at least 3 train-of-four ratio values = or > 0.9) was due to the observed trend.The analysis was performed with the LongCART package in a R shiny app (freely available at https://ppos.shinyapps.io/public/) 1  Given the observed mean difference between the study groups (431 sec), which was higher than expected, and both high conditional power values and high post-hoc estimated power of the trial, the Steering Committee considered the decision to discontinue the study to be correct.If enrollment continued to 266 cases, it was highly unlikely to observe a statistically significant difference in the primary endpoint compared to the results obtained from the analysis of the recruited patients.

1 .
Placement of two pediatric electrodes 3-4 cm apart on the course of the ulnar nerve near the wrist of the limb contralateral to the surgical site 2. Application of accelerometric sensor to the thumb employing the appropriate Hand Adapter device (Organon Teknika BV, Boxtel, Holland) 3. Application of 10 single twitch stimuli at 1Hz using an intensity of 50 mA verifying the correct motor response to the electrical stimulus 4. Application of tetanic stimulation at 50Hz for 5 seconds 5. Calibration of the device using the CAL2 algorithm 6. Start of continuous stimulation at a frequency of 1Hz 7. If twitch values (T1) were maintained within the 95-105% range after 3 minutes, rocuronium could be administered 8.If T1 values deviated from the 95-105% range, it was necessary to recalibrate the device starting again from "step 5" t tests -Means: Difference between two independent means (two groups) Tail(s) = One, Effect size d = 0,902605, Allocation ratio N2/N1 = 1,05882, α err prob = 0,05 Total sample size

Plot of power vs. sample size:
. The analysis result is reported below: Kundu, M.G., Samanta, S. & Mondal, S. (2023) Review of calculation of conditional power, predictive power and probability of success in clinical trials with continuous, binary and time-to-event endpoints.Health Serv Outcomes Res Method.[Greyline: power of 90%; orange line: number of recruited patients; blue line: planned sample size] SE, standard error; * Achieving threshold of 300 sec; ° Achieving statistical significance at 1-sided 0.05 level A post-hoc power analysis was also performed on the same data using a one tailed 1 2 Faul, F., Erdfelder, E., Buchner, A., & Lang, A.-G. (2009).Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses.Behavior Research Methods, 41, 1149-1160